In vitro studies of phospholipid-modified PAMAM-siMDR1 complexes for the reversal of multidrug resistance in human breast cancer cells

[Display omitted] The application of RNAi therapeutics is promising in combating several major human diseases including malignant tumors. However, this approach is limited due to its delivery barriers. In this study, we designed a new carrier system loaded with a functional siRNA targeting MDR1 gene...

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Bibliographic Details
Published in:International journal of pharmaceutics 2017-09, Vol.530 (1-2), p.291-299
Main Authors: Liu, Jing, Li, Jun, Liu, Nan, Guo, Nana, Gao, Chen, Hao, Yanli, Chen, Lei, Zhang, Xiaoning
Format: Article
Language:English
Subjects:
ATP Binding Cassette Transporter, Sub-Family B - genetics
Breast cancer
Breast Neoplasms - drug therapy
Cell Line, Tumor
Dendrimers - chemistry
Doxorubicin - administration & dosage
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Humans
MCF-7 Cells
Multidrug resistance
Phospholipid (PL)
Phospholipids - chemistry
RNA Interference
siRNA delivery
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Summary:[Display omitted] The application of RNAi therapeutics is promising in combating several major human diseases including malignant tumors. However, this approach is limited due to its delivery barriers. In this study, we designed a new carrier system loaded with a functional siRNA targeting MDR1 gene to reverse multi-drug resistance (MDR) in human breast cancer MCF-7/ADR cells. Phospholipid-modified PAMAM-siMDR1 complexes were designed on the external decoration of polyamidoamine (PAMAM) with phospholipid (PL) and the electrostatical interaction between PAMAM and siMDR1 to form hybrid nanocomplexes (PL-dendriplexes). Compared with siMDR1 and dendriplexes (PAMAM-siMDR1), this delivery system represented higher gene silencing efficiency, enhanced cellular uptake of siMDR1, decreased p-gp expression, raised cellular accumulation of doxorubicin (DOX) and inhibited the tumor cell migration. Moreover, the siMDR1 loaded PL-dendriplexes worked synergistically with paclitaxel (PTX) for treating MDR, leading to increased cell apoptosis and cell phase regulation. Overall, this study shows that the PL-dendriplexes hold great promise in reversing the drug-resistance in MCF-7/ADR cells.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2017.06.026